目的:探讨白细胞介素-18(IL-18) 对人肺癌裸鼠皮下移植瘤生长的影响及抗肿瘤机制.方法:采用荷人肺腺癌A549细胞的裸鼠皮下移植瘤模型,不同剂量(5μg/100μl、50μg/100μl) 的IL-18 进行腹腔内注射,对照组为磷酸盐缓冲液(PBS溶液),观察瘤细胞生长能力和裸鼠生存期,应用光学显微镜观察肿瘤组织形态学变化,TUNEL法观察肿瘤细胞凋亡情况.结果:与对照组比较,IL-18高剂量组和IL-18常规剂量组明显抑制了皮下移植瘤生长(P＜0.05).IL-18常规剂量组生存期(63±8天)明显延长(P＜0.05),IL-18高剂量组(44±5天)与空白对照组(42±6天)生存期无明显差异( P＞0.05).IL-18常规剂量治疗组和IL-18高剂量治疗组肿瘤组织内见大量淋巴细胞及炎细胞浸润,可见肿瘤细胞点、片状坏死;IL-18高剂量组和IL-18常规剂量组的凋亡细胞数均明显高于空白对照组(P＜0.01).结论:IL-18 在裸鼠体内具有明显的抗肿瘤作用,其机制可能是刺激淋巴细胞、NK细胞和吞噬细胞等炎细胞分泌各种细胞因子,诱导肿瘤细胞凋亡,发挥抗肿瘤作用.%Objective :To investigate the antitumor activity of IL - 18 in nude mice bearing lung adenocarcinoma A549 cell xenografts and to discuss the mechanism of antitumor activity of IL - 18. Methods: Eighteen nude mice with lung adenocarcinoma A549 cell xenografts were randomly divided into 3 groups. Two groups received intraperitoneal injection of IL - 18 at various doses ( 5 and 50 mg/lOOμl) and the control group received intraperitoneal injection of PBS for 20 days. Then, to observe the grow activity of tumor and the survival time of nude mice. The morphology and apoptosis of specimen were observed by light microscopy and TUNEL. Results : IL - 18 of general dose group and high dose group caused the growth of tumors slowly in vivo( P ＜0. 05 ). The survival time of nude mice in general dose group( 63 ±8d ) was much longer than that of high dose group( 44 ± 5d ) and control group( 42 ±6d )( P ＜ 0. 05 ). There were more lymphocyte ,inflammatory cells and necrosis in tumor tissues of general dose group and high dose group than control group. There existed apoptotic cells in general dose group and high dose group. Apoptotic in- dex was significantly higher in treatment group than that in control group ( P ＜0. 01 ). Conclusion: IL - 18 had remarkable antitumor activity in nude mice bearing lung adenocarcinoma A549 cell xenografts. It may be involved in its antitumor mechanism that IL - 18 induced of IFN - γ production and the promotion of different effector cells ,then induced tumor cell apoptosis.
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